Thal can effectively prevent skin and pulmonary tissue fibrosis in a mouse model of SSc through the TGF-β1/Smad3 signaling pathway and can rectify the distortion of the Th17/Treg balance in SSc by potentially regulating Th17 and Treg cell production, as well as their related factors expression.
The aim of this study was to assess the serum content of TGF-β1 in patients with systemic sclerosis and to assess its potential role in tissue fibrosis.
TGF-β1 (alone or in combination with EGF) only can upregulate AQP3 expression in SSc fibroblasts so, TGF-β1 affect MMP-1 and MMP-9 just in SSc fibroblasts.
Stimulation with transforming growth factor β1 (TGFβ1) inhibited apelin expression in fibroblasts, suggesting that activation of TGFβ1 signaling in SSc might be responsible for reduced apelin expression in SSc fibroblasts.
5-HT<sub>2</sub> and 5-HT<sub>2B</sub> antagonists attenuate pro-fibrotic phenotype in human adult dermal fibroblasts by blocking TGF-β1 induced non-canonical signaling pathways including STAT3 : implications for fibrotic diseases like scleroderma.
PKG1 and 2 are upregulated in SSc in a transforming growth factor-β1 (TGFβ1)-dependent manner, as an attempt to compensate for the decreased signalling through the sGC-cGMP-PKG pathway.
Although ductal epithelial TGF-β1 expression was similar between the groups (P = 0.345), acinar cell expression was found to be more frequent in the SSc (72.7%) and overlap patients (85.7%) in comparison with the SS cases (58.2%; P = 0.004).
In the present study, the effect of asiatic acid (AA) on SSc-associated pulmonary fibrosis (PF) and its association with the transforming growth factor-β1 (TGF-β1)/Smad2/3 signaling pathway were evaluated.
TGF-β1 initiated myofibroblast differentiation in both cell types, yet with striking phenotypic and functional differences: In relation to H-MSC-derived myofibroblasts induced by TGF-β1, those obtained from SSc-MSCs expressed more contractile proteins, migrated towards TGF-β1, had low proliferative capacity, and secreted higher amounts of collagen paralleled by reduced MMP expression.
The aim of this study was to evaluate whether TGF-β1 and inhibition of c-Abl influence Bax to Bcl-2 ratio and apoptosis in SSc and healthy dermal fibroblasts.
To investigate whether TGF-β1 gene promoter polymorphisms were associated with the susceptibility of SSc, we performed a meta-analysis based on all available studies through PubMed, Elsevier Science Direct, Embase, and Chinese Biomedical, China National Knowledge Infrastructure and Google Scholar with the last report up to March 15, 2013.
We found that bp -532 to -521 on the VEGF promoter is a putative binding site for Smads, and that the binding activity of Smad3 to VEGF promoter was constitutively increased in SSc fibroblasts as well as in normal fibroblasts treated with exogenous TGF-β1.
This study shows that the increased number of macrophages with heterogeneous immunophenotypes, which might be induced by MCP-1 and CSF-1, could participate in the sclerotic lesion formation, presumably through increased fibrogenic factors such as galectin-3 and TGF-β1; the data may provide useful information to understand the pathogenesis of the human scleroderma condition.
IL-17A signaling is suppressed due to the downregulation of the receptor by the intrinsic activation of TGF-β1 in SSc fibroblasts, which may amplify the increased collagen accumulation and fibrosis characteristic of SSc.
Furthermore, we found the c-met promoter contains a putative binding site for Smads, and the binding activity of Smad2/3 to the c-met promoter was constitutively up-regulated in SSc fibroblasts as well as in normal fibroblasts treated with exogenous TGF-β1.
The applicability of these findings to TGFβ1-driven fibrosis in humans was examined in patients with scleroderma-related interstitial lung disease (ILD).